LOW-DENSITY LIPOPROTEIN TURNOVER STUDIES IN MAN - EVALUATION OF THE INTEGRATED RATE EQUATIONS METHOD, USE OF A WHOLE-BODY RADIOACTIVITY COUNTER, AND THE PROBLEM OF PARTIAL DENATURATION

We studied the turnover of low-density lipoprotein, density 1.031-1.056 kg/l, in five normal subjects and in four subjects with hyperlipoproteinemia, using as tracer low-density lipoprotein labelled in the protein moiety with 131I. We analysed data derived with and without a whole-body radioactivity counter. Four models were used, including the integrated rate equations of Nosslin. In most patients all methods gave similar results for the fractional catabolic rate. Use of the integrated rate equations allowed us to calculate the fractional catabolic rate in 3-5 days compared with 12 days for a multicompartmental method using plasma activity alone. The integrated rate equations method was valid only in a steady metabolic state, and could apparently be used when there was minor tracer denaturation. It was probably invalid when there was major partial tracer denaturation. The degree of partial denaturation could be estimated from the whole-body radioactivity graph. The whole-body counter was quick to use, required low levels of radioactivity and avoided error-prone urine collection. Estimates of the relative size of the intra-vascular and extravascular compartments derived by five different methods were similar in studies in which there was insignificant denaturation of tracer.